Biomedical subjects
Publications and source records attributed to Andrea Giachetti.
We report on our work on the development of a novel holographic display technology, capable of targeting multiple freely moving naked eye viewers, and of a demonstrator, exploiting this technology to provide medical specialists with a truly interactive collaborative 3D environment for diagnostic discussions and/or pre-operative planning.
A combination of in silico tools and experimental NMR data is proposed for relatively fast determination of protein-ligand structural models and demonstrated from known inhibitors of matrix metalloproteinases (MMP). The 15N 1H heteronuclear single quantum coherence (HSQC) spectral assignment and the 3D structure, either X-ray or NMR, are needed. In this method, the HSQC spectrum with or without the ligand is used to determine the interaction region of the ligand. Docking calculations are then performed to obtain a set of structural models. From the latter, the nuclear Overhauser effects (NOEs) between the ligand and the protein can be predicted. Guided by these predictions, a number of NOEs can be detected and assigned through a HSQC NOESY experiment. These data are used as structural restraints to reject/refine the initial structural models through further in silico work. For a test protein (MMP-12, human macrophage metalloelastase), a final structure of a protein-ligand adduct was obtained that matches well with the full structural determination. A number of structural predictions were then made for adducts of a similar protein (MMP-1, human fibroblast collagenase) with the same and different ligands. The quality of the final results depended on the type and number of experimental NOEs, but in all cases, a well-defined ligand conformation in the protein binding site was obtained. This protocol is proposed as a viable alternative to the many approaches described in the literature.
The study describes the application of a web-based software in the planning of the endovascular treatment of abdominal aortic aneurysms (AAA). The software has been developed in the framework of a 2-year research project called Aneurysm QUAntification Through an Internet Collaborative System (AQUATICS); it allows to manage remotely Virtual Reality Modeling Language (VRML) models of the abdominal aorta, derived from multirow computed tomography angiography (CTA) data sets, and to obtain measurements of diameters, angles and centerline lengths. To test the reliability of measurements, two radiologists performed a detailed analysis of multiple 3D models generated from a synthetic phantom, mimicking an AAA. The system was tested on 30 patients with AAA; CTA data sets were mailed and the time required for segmentation and measurement were collected for each case. The Bland-Altman plot analysis showed that the mean intra- and inter-observer differences in measures on phantoms were clinically acceptable. The mean time required for segmentation was 1 h (range 45-120 min). The mean time required for measurements on the web was 7 min (range 4-11 min). The AQUATICS web server may provide a rapid, standardized and accurate tool for the evaluation of AAA prior to the endovascular treatment.
Modules that use paramagnetism-based NMR restraints have been developed and integrated in the well known program for solution structure determination Xplor-NIH; the complete set of such modules is called PARArestraints for Xplor-NIH. Paramagnetism-based restraints are paramagnetic relaxation enhancements, pseudocontact shifts, residual dipolar couplings due to metal and overall magnetic anisotropy, and cross correlation between Curie relaxation and nuclear-nuclear dipolar relaxation. The complete program has been tested by back-calculating NOEs and paramagnetism-based restraints from the X-ray structure of cytochrome c (553) from B. pasteurii. Furthermore, the same experimental restraints previously used to determine the solution structure of cytochrome c (553) itself, of cytochrome b (5), and of calbindin D(9k) with the program PARAMAGNETIC DYANA, have been used for structure calculations by using PARArestraints for Xplor-NIH. The agreement between the two programs is quite satisfactory and validates both protocols.
In this article, a description of the statistics and dynamics of cytochrome b(5) in both reduced and oxidized forms is given. Results of molecular dynamics computer simulations in the explicit solvent have been combined with mode-coupling diffusion models including and neglecting the molecule-solvent correlations. R(1) and R(1 rho) nuclear magnetic relaxation parameters of (15)N in the protein backbone have been calculated and compared with experiments. Slight changes in charge density in the heme upon oxidation produces a cascade of changes in charge distributions from heme propionates up to charged residues approximately 1.5 nm from Fe. These changes in charge distributions modify the molecular surface and the water shell surrounding the protein. The statistical changes upon oxidation can be included in diffusive models that physically explain the upper and lower limits of R(1 rho) relaxation parameters at high off-resonance fields.
We describe a strategy for collecting experimental data and validating a bone-burr haptic contact model developed in a virtual surgical training system for middle ear surgery. The validation strategy is based on the analysis of data acquired during virtual and real burring sessions. Our approach involves intensive testing of the surgical simulator by expert surgeons and trainees as well as experimental data acquisition in a controlled environment.
Mastoidectomy is one of the most common surgical procedures relating to the petrous bone. In this paper we describe our preliminary results in the realization of a virtual reality mastoidectomy simulator. Our system is designed to work on patient-specific volumetric object models directly derived from 3D CT and MRI images. The paper summarizes the detailed task analysis performed in order to define the system requirements, introduces the architecture of the prototype simulator, and discusses the initial feedback received from selected end users.